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Biomedical subjects

X L Yang

Publications and source records attributed to X L Yang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Melatonin modulates gamma-aminobutyric acid(A) receptor-mediated currents on isolated carp retinal neurons.

Modulation by melatonin of gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated responses was studied in bipolar and amacrine-like cells acutely isolated from carp retina, using the whole-cell patch-clamp technique. Melatonin of 1 mM accelerated desensitization of the GABA(A) receptors at both bipolar and amacrine-like cells. In addition, 1 mM melatonin hardly changed the GABA(A) receptor-mediated response amplitude of bipolar cells, while it increased or decreased that of amacrine-like cells, depending on the concentration of GABA applied. These modulatory effects, which can not be blocked by luzindole, a melatonin receptor antagonist, may be due to the allosteric action caused by melatonin bound to a site of the GABA(A) receptors.

Animals↗
PubMed2001

Forskolin modulation of desensitization at GABA(A) and glycine receptors is not mediated by cAMP-dependent protein kinase in isolated carp amacrine-like cells.

The effects of forskolin on gamma-aminobutyric acid type-A (GABA(A)) and glycine receptors in amacrine-like cells of carp (Carassius auratus) retina were studied using patch-clamp techniques. Application of 50 microM forskolin markedly accelerated the desensitization of whole-cell responses induced by 100 microM GABA or glycine without changing the peak amplitude of the response. Both 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and 3-isobutyl-1 -methylxanthine (IBMX) (500 microM) failed to accelerate the desensitization of these two receptors. Protein kinase A (PKA) inhibitors, N- [2-[(p-bromocinnamyl)amino]ethyl)-5-isoquinolinesulfonamide dihydrochloride (H-89) and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-8), could not block these effects of forskolin. An inactive analogue of forskolin, 1,9-dideoxyforskolin (DFSK), accelerated the desensitization effectively. These results suggest that forskolin's effects are not mediated by activation of the PKA pathway. Moreover, similar results were obtained using excised outside-out patches of these cells, suggesting that forskolin may act on an extracellular site(s). The neurosteroids 5alpha-pregnane-3alpha,21 -diol-20-one (THDOC) and 5-pregnen-31 -ol-20-one sulfate sodium (PS), structural analogues of forskolin, accelerated the desensitization of these receptors without changing the peak amplitudes, thus mimicking forskolin's effects. Furthermore, PS interacted with forskolin on these receptors so as to slow down the responses. These results raise the possibility that forskolin acts directly on an extracellular site(s) of the GABA(A) and glycine receptors, shared with neurosteroids, in carp amacrine-like cells.

Animals↗
PubMed2001

Signals from cone photoreceptors to L-type horizontal cells are differentially modulated by low calcium in carp retina.

Ca2+ plays crucial roles in both phototransduction and calcium-dependent glutamate release from the photoreceptor terminal. Modulation, by lowering extracellular Ca2+, of red-sensitive (R-) and short wavelength-sensitive (S-) cone-driven light responses of L-type horizontal cells (LHCs) was studied in the isolated superfused carp retina using intracellular recording techniques. Low Ca2+ (nominally Ca2+-free) Ringer's reduced responses of LHCs to both green (500 nm) and red (680 nm) flashes in darkness, with the former being suppressed more substantially than the latter. This differential suppression became more significant when contribution of R-cones to the green-light-induced responses was diminished by a moderate red (680 nm) background light. Application of IBMX, an inhibitor of phosphodiesterase (PDE), increased LHC responses to both red and green flashes equally, resembling the effect of low Ca2+ on phototransduction. In addition, photopic electroretinographic P III responses, reflecting the activity of cones, to red flashes were more potentiated by low Ca2+, compared to those to green flashes, whilst they were both equally potentiated by IBMX. Furthermore, low Ca2+ caused a more pronounced suppression of LHC responses to red flashes than those to green flashes in the presence of IBMX. It is postulated that reduction of LHC responses in low Ca2+ may be due to the 'saturation suppression' caused by the increased glutamate release from the photoreceptor terminal and the differential modulation may reflect a consequence of the dual action of low Ca2+ on the PDE activity in the photoreceptor outer segment and the synaptic strength between cones and LHCs.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver.

Previously, retinoblastoma (Rb) transgenic mice were produced under the control of the Rb gene promoter and showed dwarf characteristics. Here, we created transgenic mice, in which the human Rb gene was controlled by the hepatocyte nuclear factor-1 gene promoter/enhancer and was expressed primarily in the liver. The liver of these novel transgenic mice was normally developed. Intriguingly, these mice showed resistance to fulminant hepatitis induced by anti-Fas antibody as well as resistance to chemical carcinogenesis in the liver. These results show that the Rb protein acts as an anti-apoptotic and anti-oncogenic agent in vivo. Our novel construct may be useful as a gene cassette in gene therapy for prevention of fulminant hepatitis and hepatoma.

Animals↗
PubMed2001

[Zinc ions: an endogenous neuromodulator].

Zinc ions are widely distributed in the central nervous system. Zinc ions are released from neurons in a calcium-dependent manner. In recent years abundant evidence indicates that zinc ions modulate not only the release of transmitters, but also the voltage- and ligand (excitatory and inhibitory amino acids)-gated channels, suggesting that these ions may serve as an important endogenous neuromodulator.

Animals↗
PubMed2001

[Studies on the properties of energy upconversion of the rare earth ErYb and HoYb in the oxyfluoride glass].

Er and Yb, Ho and Yb codoped in the oxyfluoride were burnt on in the specific temperature, and got two kinds of samples. Using 930 nm as an exciting light, the emitting fluorescent spectra of two kinds of the samples were measured, and observed the red band and green band fluorescent spectra, respectively. According to the detected absorption spectra of Er2O3, Ho2O3, Yb2O3 and the rule of energy jump, the mechanism and the properties of the energy upconversion of two kinds of the samples were explained. As can be seen, energy upconversion properties were determined mainly by the absorbtion spectra of Er2O3, Yb2O3. Energy upconversion efficiency were determined by excitative photons.

Energy Transfer↗
PubMed2000

Binding of a macrocyclic bisacridine and ametantrone to CGTACG involves similar unusual intercalation platforms.

The binding of a macrocyclic bisacridine and an antitumor intercalator ametantrone to DNA has been studied. We carried out X-ray diffraction analyses of the complexes between both intercalators and CGTACG. We have determined the crystal structure, by the multiple-wavelength anomalous diffraction (MAD) method, of bisacridine complexed with CGTA[br(5)C]G at 1.8 A resolution. The refined native crystal structure at 1.1 A resolution (space group C222, a = 29.58 A, b = 54.04 A, c = 40.22 A, and R-factor = 0.163) revealed that only one acridine of the bisacridine drug binds at the C5pG6 step of the DNA, with the other acridine plus both linkers completely disordered. Surprisingly, both terminal G.C base pairs are unraveled. The C1 nucleotide is disordered, and the G2 base is bridged to its own phosphate P2 through a hydrated Co(2+) ion. G12 is swung toward the minor groove with its base stacked over the backbone. The C7 nucleotide is flipped away from the duplex part and base paired to a 2-fold symmetry-related G6. The central four base pairs adopt the B-DNA conformation. An unusual intercalator platform is formed by bringing four complexes together (involving the 222 symmetry) such that the intercalator cavity is flanked by two sets of G x C base pairs (i.e., C5 x G8 and G6 x C7) on each side, joined together by G6 x G8 tertiary base pairing interactions. In the bisacridine-CGTACG complex, the intercalation platform is intercalated with two acridines, whereas in the ametantrone-CGTACG complex, only one ametantrone is bound. NMR titration of the bisacridine to AACGATCGTT suggests that the bisacridine prefers to bridge more than one DNA duplex by intercalating each acridine to different duplexes. The results may be relevant in understanding binding of certain intercalators to DNA structure associated with the quadruplet helix and Holliday junction.

Acridines↗
PubMed2000

MFH-1 is required for bone morphogenetic protein-2-induced osteoblastic differentiation of C2C12 myoblasts.

Mesenchyme forkhead-1 (MFH-1), a winged helix/forkhead transcription factor, is expressed in developing cartilaginous tissues, kidney and arch arteries, and is essential for the normal development of the axial skeleton and aortic arch formation of mice. To investigate the possible role of MFH-1 in osteogenesis and osteoblast differentiation, we examined expression of MFH-1 induced by bone morphogenetic protein-2 (BMP-2) in C2C12 myoblasts, and found that MFH-1 protein and also MFH-1 mRNA increased markedly in C2C12 cells after treatment with BMP-2. To confirm the hypothesis that BMP-2 induced osteoblastic differentiation of C2C12 cells by increasing MFH-1 expression, we lowered the endogenous MFH-1 level by stably transfecting C2C12 cells with antisense MFH-1 sequence, and found that in antisense MFH-1 cell lines, both alkaline phosphatase (ALP) activity and production of osteocalcin induced by BMP-2 decreased markedly in comparison with control cell lines. Our results suggest that the BMP-2-induced MFH-1 protein may play a key role in regulating the commitment to osteoblastic differentiation of C2C12 myoblasts and production of osteoblast markers including ALP and osteocalcin.

Animals↗
PubMed2000

Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance.

The accumulation of cisplatin is decreased in many cisplatin-resistant cell lines, and an active efflux pump for cisplatin exists in some of them, but it has not yet been identified. In this study, we transfected the copper-transporting P-type ATPase cDNA (ATP7B) into human epidermoid carcinoma KB-3-1 cells. The transfectant, KB/WD cell line, which overexpressed the P-type ATPase, ATP7B, was resistant to both cisplatin (8.9-fold) and copper (2.0-fold). The accumulation of cisplatin in KB/WD cells was lower than in mock-transfected KB/CV cells, and the efflux of cisplatin from KB/WD cells was enhanced compared with KB/CV cells. KB/WD cells were sensitive to other heavy metals, such as antimony, arsenate, arsenite, cadmium, and cobalt. ATP7B was overexpressed in cisplatin-resistant prostate carcinoma PC-5 cells but not in the parental PC-3 cells and the revertant PC-5R cells. ATP7B may be involved in cisplatin resistance in some tumors.

Adenosine Triphosphatases↗
PubMed2000

Effects of extracts from sporoderm-broken spores of Ganoderma lucidum on HeLa cells.

The effects of extracts from Ganoderma lucidum spores on the growth of human cervix uteri tumor HeLa cells as well as on the cell cycle and intracellular calcium level were investigated. Alcohol extracts were prepared from sporoderm-broken and sporoderm-nonbroken spores (termed extract I and extract II) of G. lucidum. Extract I was then subjected to silica gel chromatography to obtain extract III. Cytotoxicity was examined by means of trypan blue exclusion and MTT tests. It was found that extract I and extract III, but not extract II strongly inhibited the growth of HeLa cells, and that extract III was more effective than extract I. Moreover, extract III was shown to be capable of blocking the cell cycle at the transition from G1 to S phase and inducing a marked decrease of intracellular calcium level, determined by flow cytometry and the specific fluorescent calcium probe Fura-2, respectively. These results imply that (1) the breaking of G. lucidum spores improves the release of cytotoxic activity and (2) the effective extract might influence the cell cycle and cellular signal transduction by altering the calcium transport system.

Calcium↗
PubMed2000

Nephrotoxicity of high- and low-osmolar contrast media. The protective role of amlodipine in a rat model.

PURPOSE: To evaluate the nephrotoxicity of high- and low-osmolar contrast media (HOCM, LOCM) on kidneys in Sprague-Dawley rats. The protective role of amlodipine was studied. MATERIAL AND METHODS: Forty rats of both sexes were randomly divided into 5 groups (n=8/group) and glycerine for inducing renal failure was given to all rats except controls. RESULTS: In diatrizoate-injected rats, blood urea nitrogen (BUN) and serum creatinine (SCr) were increased; levels of phospholipase A2 (PLA2), lipid peroxide (LPO) and calcium were also increased in renal tissues. There was no significant difference between LOCM (iohexol) animals and glycerol controls either in the renal levels of PLA2, LPO and calcium or in the levels of BUN and SCr. The histologic changes were milder in the LOCM animals than in the HOCM animals. In the group pretreated with amlodipine, no increase in the levels of BUN or SCr was discovered and the renal content of PLA2, LPO and calcium were significantly lower than in the HOCM group; the renal injuries induced by diatrizoate were alleviated. CONCLUSION: The HOCM, diatrizoate, was more toxic to rat kidneys than the LOCM iohexol; PLA2, LPO and calcium load played a role in producing renal function impairment induced by diatrizoate meglumine; amlodipine protected the renal tissue from nephrotoxicity induced by diatrizoate.

Acute Kidney Injury↗
PubMed2000

Subcellular localization and complements of GABA(A) and GABA(C) receptors on bullfrog retinal bipolar cells.

gamma-Aminobutyric acid (GABA) receptors on retinal bipolar cells (BCs) are highly relevant to spatial and temporal integration of visual signals in the outer and inner retina. In the present work, subcellular localization and complements of GABA(A) and GABA(C) receptors on BCs were investigated by whole cell recordings and local drug application via multi-barreled puff pipettes in the bullfrog retinal slice preparation. Four types of the BCs (types 1-4) were identified morphologically by injection of Lucifer yellow. According to the ramification levels of the axon terminals and the responses of these cells to glutamate (or kainate) applied at their dendrites, types 1 and 2 of BCs were supposed to be OFF type, whereas types 3 and 4 of BCs might be ON type. Bicuculline (BIC), a GABA(A) receptor antagonist, and imidazole-4-acetic acid (I4AA), a GABA(C) receptor antagonist, were used to distinguish GABA receptor-mediated responses. In all BCs tested, not only the axon terminals but also the dendrites showed high GABA sensitivity mediated by both GABA(A) and GABA(C) receptors. Subcellular localization and complements of GABA(A) and GABA(C) receptors at the dendrites and axon terminals were highly related to the dichotomy of OFF and ON BCs. In the case of OFF BCs, GABA(A) receptors were rather evenly distributed at the dendrites and axon terminals, but GABA(C) receptors were predominantly expressed at the axon terminals. Moreover, the relative contribution of GABA(C) receptors to the axon terminals was prevalent over that of GABA(A) receptors, while the situation was reversed at the dendrites. In the case of ON BCs, GABA(A) and GABA(C) receptors both preferred to be expressed at the axon terminals; relative contributions of these two GABA receptor subtypes to both the sites were comparable, while GABA(C) receptors were much less expressed than GABA(A) receptors. GABA(A), but not GABA(C) receptors, were expressed clusteringly at axons of a population of BCs. In a minority of BCs, I4AA suppressed the GABA(C) responses at the dendrites, but not at the axon terminal, implying that the GABA(C) receptors at these two sites may be heterogeneous. Taken together, these results suggest that GABA(A) and GABA(C) receptors may play different roles in the outer and inner retina and the differential complements of the two receptors on OFF and ON BCs may be closely related to physiological functions of these cells.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Effects of betaxolol on light responses and membrane conductance in retinal ganglion cells.

PURPOSE: To examine the physiological effects of betaxolol, a beta1-adrenergic receptor blocker commonly used in the treatment of glaucoma, on retinal ganglion cells and to evaluate its potential to elicit responses consistent with a neuroprotective agent against ganglion cell degeneration. METHODS: Single-unit extracellular recording, electroretinogram (ERG), intracellular and whole-cell patch-clamp recording techniques were made from flatmounted, isolated retina, superfused eyecup, and living retinal slice preparations of the larval tiger salamander. RESULTS: Bath application of 20 microM betaxolol reduced the glutamate-induced increase of spontaneous spike rate in retinal ganglion cell by approximately 30%. The glutamate-induced postsynaptic current recorded under voltage-clamp conditions was reduced by 50 microM betaxolol, and the difference current-voltage (I-V) relation (I(Control)-I(betaxolol)) was N-shaped and AP5-sensitive, characteristic of N-methyl-D-aspartate receptor-mediated current. Application of 50 microM betaxolol reversibly reduced the voltage-gated sodium and calcium currents by approximately one third of their peak amplitudes. The times-to-action of betaxolol on ganglion cells are long (15-35 minutes for 20-50 microM betaxolol), indicative of modulation through slow biochemical cascades. Betaxolol, up to 100 microM, exerted no effects on horizontal cells or the ERG, suggesting that the primary actions of this beta1 blocker are restricted to retinal ganglion cells. CONCLUSIONS: These physiological experiments provide supporting evidence that betaxolol acts in a manner consistent with preventing retinal ganglion cell death induced by elevated extracellular glutamate or by increased spontaneous spike rates under pathologic conditions. The physiological actions of betaxolol lead to reducing neurotoxic effects in ganglion cells, which are the most susceptible retinal neurons to glutamate-induced damages under ischemic and glaucomatous conditions. Therefore, betaxolol has the potential to be a neuroprotective agent against retinal degeneration in patients with disorders mediated by such mechanisms.

Adrenergic beta-Antagonists↗
PubMed2000

Changes of copper-transporting proteins and ceruloplasmin in the lentiform nuclei in primary adult-onset dystonia.

A recent study reported an increase of brain tissue copper content in the lentiform nuclei of patients with primary adult-onset dystonia. In this study we analyze copper-metabolizing proteins (Menkes protein, Wilson protein, ceruloplasmin) by Western blot analysis in frozen brain tissue (lentiform nuclei) of 3 patients with primary dystonia. Menkes protein was reduced in all patients, while Wilson protein and ceruloplasmin were increased in the 2 patients with focal dystonia and reduced in the patient with generalized dystonia. Our data provides further evidence for a disturbance of copper metabolism in primary dystonia.

Adenosine Triphosphatases↗
PubMed2000

Expression of GABA transporters on bullfrog retinal Müller cells.

gamma-Aminobutyric acid (GABA) transporters (GATs) are involved in regulating GABAergic transmission through the high-affinity uptake and release of GABA. In the present work, the expression of different subtypes of GATs (GAT-1, GAT-2, and GAT-3) on Müller cells was investigated both immunocytochemically and electrophysiologically in the bullfrog retina. Double-labeling experiments of glial fibrillary acidic protein (GFAP), a specific marker for Müller cells, and GATs showed that the somata, major processes, endfeet, and even branchlets of almost all Müller cells strongly expressed GAT-1 on the membrane, whereas the main trunks and endfeet of about 80-90% Müller cells were moderately GAT-2 labeled. No GAT-3 immunoreactivity was observed in Müller cells. Meanwhile, using the whole-cell recording technique, GAT-mediated currents were recorded from Müller cells in the retinal slice preparation, and they were reversibly blocked by removal of extracellular Na(+) and spread more or less evenly over the surface of these cells. Furthermore, the GATs on the Müller cells were sensitive to both nipecotic acid and beta-alanine, GABA uptake blockers. Taken together, the complementary immunocytochemical and electrophysiological results suggest that bullfrog Müller cells express functional GAT-1 and GAT-2, which may regulate GABAergic transmission by either taking up or releasing GABA, or both.

Animals↗
PubMed2000

[High-affinity glutamate transporters].

High-affinity glutamate transporters are located predominantly in the plasma membrane of neurons and glial cells. They have the capacity to take up glutamate from the extracellular space into the cells against its concentration gradient to terminate glutamatergic transmission and to keep the extracellular glutamate concentration at low levels to protect neurons from glutamate toxicity. As glutamate transporters were recently cloned, the research in this field has been greatly advancing. This article focuses on recent progress in the study of molecular structure, distribution of expression, physiological significance, structure-function relationships of these transporters.

Amino Acid Transport System X-AG↗